Enhanced oral paclitaxel bioavailability after administration of paclitaxel-loaded lipid nanocapsules

The aim of this study was to evaluate the pharmacokinetics of paclitaxel-loaded lipid nanocapsules (LNC) in rats to assess the intrinsic effect of the dosage form on the improvement of paclitaxel oral exposure. Paclitaxel-loaded LNC were prepared and characterized in terms of size distribution, drug...

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Bibliographic Details
Published in:Pharmaceutical research 2006-06, Vol.23 (6), p.1243-1250
Main Authors: Peltier, Sandra, Oger, Jean-Michel, Lagarce, Frédéric, Couet, William, Benoît, Jean-Pierre
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
Antineoplastic Agents, Phytogenic - administration & dosage
Antineoplastic Agents, Phytogenic - pharmacokinetics
Biological Availability
Drug Compounding
Injections, Intravenous
Intestinal Absorption
Lipids - chemistry
Liposomes
Male
Nanostructures - chemistry
Paclitaxel - administration & dosage
Paclitaxel - pharmacokinetics
Rats
Rats, Sprague-Dawley
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Summary:The aim of this study was to evaluate the pharmacokinetics of paclitaxel-loaded lipid nanocapsules (LNC) in rats to assess the intrinsic effect of the dosage form on the improvement of paclitaxel oral exposure. Paclitaxel-loaded LNC were prepared and characterized in terms of size distribution, drug payload, and the kinetics of paclitaxel crystallization. Taxol, Taxol with verapamil, or paclitaxel-loaded LNC were administered orally to rats. The plasma concentration of paclitaxel was determined using liquid chromatography mass spectrometry. The average size of LNC was 60.9 +/- 1.5 nm. The drug payload of paclitaxel was 1.91 +/- 0.01 mg/g of aqueous dispersion. The encapsulation efficiency was 99.9 +/- 1.0%, and 1.7 +/- 0.1% of paclitaxel was crystallized after 24 h. The oral bioavailability of Taxol alone was 6.5%. After oral administration of paclitaxel-loaded LNC or paclitaxel associated with verapamil, the area under the plasma concentration-time curve was significantly increased (about 3-fold) in comparison to the control group (p < 0.05). The results indicated that LNC provided a promising new formulation to enhance the oral bioavailability of paclitaxel while avoiding the use of pharmacologically active P-gp inhibitors, such as verapamil.
ISSN:0724-8741
1573-904X
DOI:10.1007/s11095-006-0022-2